The present invention relates to a process for producing solid dosage forms by molding a plastic active ingredient-containing mixture with use of a continuously operating molding tool with two parts which cooperate to mold the plastic mixture, with at least one part having a plurality of depressions to receive and mold the plastic mixture.
The production of solid dosage forms, in particular pharmaceutical dosage forms or foodstuffs or food supplements for humans and animals, by calendering an active ingredient-containing melt is disclosed in a number of publications. This process is based on the embedding of an active ingredient in a melt composed of a carrier, e.g. fatty substances or physiologically tolerated polymers. This usually entails an active ingredient-containing melt or an active ingredient-containing plastic mixture being produced in a mixer and/or extruder and then being fed into a molding tool, e.g. a calender with molding rolls. The calender comprises a pair of counter-rotating molding rolls which have on their surface engravings (depressions) which, for example, correspond to the shape of one half of a tablet. The tablet molding takes place in the region of contact of the two rolls by combination of the tablet composition in one depression on one roll with that in the opposite depression on the other roll. It is also conceivable to combine a molding roll with depressions and a smooth roll or a smooth belt to mold such plastic mixtures. The production of tablets by this process is described in general by DE-A-17 66 546 and U.S. Pat. No. 4,880,585; DE-A-44 46 467 describes the production of lenticular tablets and WO-96/19962 the production of divisible tablets. These processes have considerable advantages compared with the conventional production of dosage forms by, for example, tableting powders and granules under pressure. Thus, melt extrusion with subsequent molding by calendering combines a plurality of stages such as metering in, mixing, plasticizing, molding and singulation, in a single continuous process and thus permits a high output, constant quality and extensive freedom in the shaping, makes few demands on the treatment of the precursors and thus makes it possible to produce large numbers of items economically. These advantages are displayed fully only with really large numbers of items, because of the many parameters requiring optimization in so many stages.
There is an observable trend toward diversification in relation to the dosage and the administration form of active ingredients in many subsectors of the drugs market. This diversification is caused inter alia by increasing demands on the uniformity of the active ingredient dose, which is not as a rule ensured by divisible tablets. The provision of a large number of dosages of the same active ingredient is required, for example, when stabilizing patients on particular active ingredients, e.g. for cardiovascular disorders, when different groups of patients have different dose requirements/response times, e.g. adults/children. A large number of dosage forms differing in the dose of active ingredient is also required for active ingredients with a small therapeutic index and for active ingredients with several medical indications. Thus, for example, in the case of the active ingredient acetylsalicylic acid the dose on use in tablets for pain is 500 mg, whereas the same active ingredient is administered in a dose of only 100 mg as platelet aggregation inhibitor. It is also desirable in many cases to be able to offer several embodiments of an active ingredient preparation, e.g. divisible or nondivisible, lenticular or oblong tablets, in order to meet the requirements of different markets or contract manufacture.
The manufacture of such a large number of different dosage forms has to date been possible only by conventional tableting, with the disadvantages which are known. In addition, with conventional tableting it is possible to achieve different dosages only by different tablet formulas for separate manufacture, and the simultaneous production of different dosages/forms in one tableting machine have not previously been disclosed and is imaginable only with great difficulty.
It is an object of the present invention to provide a process and an apparatus which make it possible quickly, efficiently and cost-effectively to produce simultaneously a large number of different dosages and/or shapings of an active ingredient.
The present invention therefore relates to a process for producing solid dosage forms by molding a plastic active ingredient-containing mixture with use of a continuously operating molding tool with two parts which cooperate to mold the plastic mixture, with at least one part having a plurality of depressions to receive and mold the plastic mixture, wherein one part has at least two groups, which differ in volume and/or shape, of depressions.